PL192561B1 - Podstawione benzyloaminy, ich zastosowanie i kompozycja farmaceutyczna - Google Patents
Podstawione benzyloaminy, ich zastosowanie i kompozycja farmaceutycznaInfo
- Publication number
- PL192561B1 PL192561B1 PL329348A PL32934897A PL192561B1 PL 192561 B1 PL192561 B1 PL 192561B1 PL 329348 A PL329348 A PL 329348A PL 32934897 A PL32934897 A PL 32934897A PL 192561 B1 PL192561 B1 PL 192561B1
- Authority
- PL
- Poland
- Prior art keywords
- 6alkyl
- benzisoxazol
- hydrogen
- formula
- solution
- Prior art date
Links
- 150000003939 benzylamines Chemical class 0.000 title claims abstract description 5
- -1 amino, hydroxy Chemical group 0.000 claims abstract description 109
- 239000001257 hydrogen Substances 0.000 claims abstract description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 61
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 29
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 19
- 150000002367 halogens Chemical class 0.000 claims abstract description 19
- 125000001424 substituent group Chemical group 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000001301 oxygen Substances 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 121
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 2
- 206010002650 Anorexia nervosa and bulimia Diseases 0.000 claims description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 2
- 208000009132 Catalepsy Diseases 0.000 claims description 2
- 208000024254 Delusional disease Diseases 0.000 claims description 2
- 208000030814 Eating disease Diseases 0.000 claims description 2
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 206010033664 Panic attack Diseases 0.000 claims description 2
- 208000028017 Psychotic disease Diseases 0.000 claims description 2
- 208000020114 Schizophrenia and other psychotic disease Diseases 0.000 claims description 2
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
- 208000013200 Stress disease Diseases 0.000 claims description 2
- 206010047853 Waxy flexibility Diseases 0.000 claims description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 235000014632 disordered eating Nutrition 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000004970 halomethyl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 201000003631 narcolepsy Diseases 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 208000019906 panic disease Diseases 0.000 claims description 2
- 208000002851 paranoid schizophrenia Diseases 0.000 claims description 2
- 208000022821 personality disease Diseases 0.000 claims description 2
- 208000019899 phobic disease Diseases 0.000 claims description 2
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 2
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 208000022925 sleep disturbance Diseases 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 40
- 208000020401 Depressive disease Diseases 0.000 abstract description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 5
- 239000012453 solvate Substances 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 abstract 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 4
- 125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 abstract 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 abstract 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 2
- 125000003342 alkenyl group Chemical group 0.000 abstract 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract 2
- 125000000304 alkynyl group Chemical group 0.000 abstract 2
- 125000003118 aryl group Chemical group 0.000 abstract 2
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 2
- 125000001072 heteroaryl group Chemical group 0.000 abstract 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 2
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 abstract 2
- 229940124530 sulfonamide Drugs 0.000 abstract 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 abstract 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 abstract 1
- 238000013160 medical therapy Methods 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 147
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 136
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 105
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
- 239000000203 mixture Substances 0.000 description 77
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 73
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 46
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 41
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- 238000005481 NMR spectroscopy Methods 0.000 description 32
- 239000012044 organic layer Substances 0.000 description 31
- 239000007787 solid Substances 0.000 description 30
- 230000002829 reductive effect Effects 0.000 description 28
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 23
- 235000019341 magnesium sulphate Nutrition 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 21
- TXRRCHZIDGBYSJ-UHFFFAOYSA-N 2-(1,2-benzoxazol-3-yl)benzaldehyde Chemical compound O=CC1=CC=CC=C1C1=NOC2=CC=CC=C12 TXRRCHZIDGBYSJ-UHFFFAOYSA-N 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 18
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 17
- 239000012267 brine Substances 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 239000011347 resin Substances 0.000 description 13
- 229920005989 resin Polymers 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- 239000000463 material Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 9
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 238000003818 flash chromatography Methods 0.000 description 9
- 239000012279 sodium borohydride Substances 0.000 description 9
- 229910000033 sodium borohydride Inorganic materials 0.000 description 9
- WWEPCBKULBKDCS-UHFFFAOYSA-N 2-fluoro-n-methoxy-n-methylbenzamide Chemical compound CON(C)C(=O)C1=CC=CC=C1F WWEPCBKULBKDCS-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 150000002466 imines Chemical class 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- APDGYQVYBWGBSD-UHFFFAOYSA-N 1-bromo-2-(diethoxymethyl)benzene Chemical compound CCOC(OCC)C1=CC=CC=C1Br APDGYQVYBWGBSD-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000007429 general method Methods 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 125000002524 organometallic group Chemical group 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- MYANOPGERSSIQJ-UHFFFAOYSA-N 2-(6-chloro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound N=1OC2=CC(Cl)=CC=C2C=1C1=CC=CC=C1C=O MYANOPGERSSIQJ-UHFFFAOYSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 5
- DQEUYIQDSMINEY-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C=C DQEUYIQDSMINEY-UHFFFAOYSA-M 0.000 description 5
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 5
- 239000002808 molecular sieve Substances 0.000 description 5
- 239000002798 polar solvent Substances 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 5
- SEISRZQKXBZVCG-UHFFFAOYSA-N 2,5-difluoro-n-methoxy-n-methylbenzamide Chemical compound CON(C)C(=O)C1=CC(F)=CC=C1F SEISRZQKXBZVCG-UHFFFAOYSA-N 0.000 description 4
- DHPSVWWHCBZFLP-UHFFFAOYSA-N 2-bromo-1-(diethoxymethyl)-4-fluorobenzene Chemical compound CCOC(OCC)C1=CC=C(F)C=C1Br DHPSVWWHCBZFLP-UHFFFAOYSA-N 0.000 description 4
- IVYGPMQYLKQFNP-UHFFFAOYSA-N 4-methyl-2,6,7-trioxabicyclo[2.2.2]octane Chemical compound C1OC2OCC1(C)CO2 IVYGPMQYLKQFNP-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-L Oxalate Chemical compound [O-]C(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-L 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- ZPIRRBYBHGWDRV-UHFFFAOYSA-N [2-(6-fluoro-1,2-benzoxazol-3-yl)phenyl]-phenylmethanone Chemical compound N=1OC2=CC(F)=CC=C2C=1C1=CC=CC=C1C(=O)C1=CC=CC=C1 ZPIRRBYBHGWDRV-UHFFFAOYSA-N 0.000 description 4
- PJQKEGSMTMAYPS-UHFFFAOYSA-N [2-(diethoxymethyl)phenyl]-(2-fluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC=CC=C1C(=O)C1=CC=CC=C1F PJQKEGSMTMAYPS-UHFFFAOYSA-N 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 150000004678 hydrides Chemical class 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 150000002905 orthoesters Chemical class 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
- GHLOTOLVNNONDS-UHFFFAOYSA-N (4-chloro-2-fluorophenyl)-[2-(diethoxymethyl)phenyl]methanone Chemical compound CCOC(OCC)C1=CC=CC=C1C(=O)C1=CC=C(Cl)C=C1F GHLOTOLVNNONDS-UHFFFAOYSA-N 0.000 description 3
- WBWOPMKSGUSGIZ-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]ethanamine;hydrochloride Chemical compound Cl.CC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 WBWOPMKSGUSGIZ-UHFFFAOYSA-N 0.000 description 3
- IUIQFAFNPZXCBL-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]ethanol Chemical compound CC(O)C1=CC=CC=C1C1=NOC2=CC=CC=C12 IUIQFAFNPZXCBL-UHFFFAOYSA-N 0.000 description 3
- JGGYFFMOVGYCDX-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]ethanone Chemical compound CC(=O)C1=CC=CC=C1C1=NOC2=CC=CC=C12 JGGYFFMOVGYCDX-UHFFFAOYSA-N 0.000 description 3
- CBYQEJJGMLIWMW-UHFFFAOYSA-N 1-bromo-2-(diethoxymethyl)-4-fluorobenzene Chemical compound CCOC(OCC)C1=CC(F)=CC=C1Br CBYQEJJGMLIWMW-UHFFFAOYSA-N 0.000 description 3
- PJMWTTMOXWPIRW-UHFFFAOYSA-N 2-(1-methylindazol-3-yl)benzaldehyde Chemical compound C12=CC=CC=C2N(C)N=C1C1=CC=CC=C1C=O PJMWTTMOXWPIRW-UHFFFAOYSA-N 0.000 description 3
- PXMPCSSNJZZAJR-UHFFFAOYSA-N 2-(6-fluoro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound N=1OC2=CC(F)=CC=C2C=1C1=CC=CC=C1C=O PXMPCSSNJZZAJR-UHFFFAOYSA-N 0.000 description 3
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 3
- NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- GYECROLIZPLTMN-UHFFFAOYSA-N 4-chloro-2-fluoro-n-methoxy-n-methylbenzamide Chemical compound CON(C)C(=O)C1=CC=C(Cl)C=C1F GYECROLIZPLTMN-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical group OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- HZFDKBPTVOENNB-GAFUQQFSSA-N N-[(2S)-1-[2-[(2R)-2-chloro-2-fluoroacetyl]-2-[[(3S)-2-oxopyrrolidin-3-yl]methyl]hydrazinyl]-3-(1-methylcyclopropyl)-1-oxopropan-2-yl]-5-(difluoromethyl)-1,2-oxazole-3-carboxamide Chemical compound CC1(C[C@@H](C(NN(C[C@H](CCN2)C2=O)C([C@H](F)Cl)=O)=O)NC(C2=NOC(C(F)F)=C2)=O)CC1 HZFDKBPTVOENNB-GAFUQQFSSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 3
- XMOURLICDSXKGC-UHFFFAOYSA-N [2-(1,2-benzoxazol-3-yl)phenyl]methanol Chemical compound OCC1=CC=CC=C1C1=NOC2=CC=CC=C12 XMOURLICDSXKGC-UHFFFAOYSA-N 0.000 description 3
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- 239000002274 desiccant Substances 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 3
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 230000008570 general process Effects 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 3
- 150000002923 oximes Chemical class 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- TVAQKPOCPLOHKU-UHFFFAOYSA-N (4-chloro-2-fluorophenyl)-[2-(diethoxymethyl)-4-fluorophenyl]methanone Chemical compound CCOC(OCC)C1=CC(F)=CC=C1C(=O)C1=CC=C(Cl)C=C1F TVAQKPOCPLOHKU-UHFFFAOYSA-N 0.000 description 2
- KKVIGLAEPYIGJS-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-2-(4-fluorophenyl)ethanamine;hydrochloride Chemical compound Cl.C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C(N)CC1=CC=C(F)C=C1 KKVIGLAEPYIGJS-UHFFFAOYSA-N 0.000 description 2
- LDWQSOCRDRZSJE-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC1=CC=CC=C1C1=NOC2=CC=CC=C12 LDWQSOCRDRZSJE-UHFFFAOYSA-N 0.000 description 2
- FGESCCXVHDSWBF-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n-[[2-(1,2-benzoxazol-3-yl)phenyl]methyl]methanamine Chemical compound C1=CC=C2C(C3=CC=CC=C3CNCC=3C(=CC=CC=3)C=3C4=CC=CC=C4ON=3)=NOC2=C1 FGESCCXVHDSWBF-UHFFFAOYSA-N 0.000 description 2
- KDHRJLQXMOBXRV-UHFFFAOYSA-N 1-bromo-3-(diethoxymethyl)benzene Chemical compound CCOC(OCC)C1=CC=CC(Br)=C1 KDHRJLQXMOBXRV-UHFFFAOYSA-N 0.000 description 2
- BFSNEBVTOODGHZ-UHFFFAOYSA-N 1-bromo-4-(diethoxymethyl)benzene Chemical compound CCOC(OCC)C1=CC=C(Br)C=C1 BFSNEBVTOODGHZ-UHFFFAOYSA-N 0.000 description 2
- BVZHAPSCOYXAMU-UHFFFAOYSA-N 1-bromo-4-chloro-2-(diethoxymethyl)benzene Chemical compound CCOC(OCC)C1=CC(Cl)=CC=C1Br BVZHAPSCOYXAMU-UHFFFAOYSA-N 0.000 description 2
- UTSSEXHZQHZWED-UHFFFAOYSA-N 2,4-difluoro-n-methoxy-n-methylbenzamide Chemical compound CON(C)C(=O)C1=CC=C(F)C=C1F UTSSEXHZQHZWED-UHFFFAOYSA-N 0.000 description 2
- HAGRVLNZAGKTAQ-UHFFFAOYSA-N 2-(1,2-benzoxazol-3-yl)-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(C=2C3=CC=CC=C3ON=2)=C1 HAGRVLNZAGKTAQ-UHFFFAOYSA-N 0.000 description 2
- TZXZGFVNRMFJSE-UHFFFAOYSA-N 2-(1,2-benzoxazol-3-yl)-5-chlorobenzaldehyde Chemical compound O=CC1=CC(Cl)=CC=C1C1=NOC2=CC=CC=C12 TZXZGFVNRMFJSE-UHFFFAOYSA-N 0.000 description 2
- VJTCTVTZJGGKHN-UHFFFAOYSA-N 2-(1,2-benzoxazol-3-yl)-5-fluorobenzaldehyde Chemical compound O=CC1=CC(F)=CC=C1C1=NOC2=CC=CC=C12 VJTCTVTZJGGKHN-UHFFFAOYSA-N 0.000 description 2
- NSKUSGAFNOEGIO-UHFFFAOYSA-N 2-(5-fluoro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound C12=CC(F)=CC=C2ON=C1C1=CC=CC=C1C=O NSKUSGAFNOEGIO-UHFFFAOYSA-N 0.000 description 2
- CRBBEKVLXLCCMY-UHFFFAOYSA-N 2-(6-chloro-1,2-benzoxazol-3-yl)-5-fluorobenzaldehyde Chemical compound O=CC1=CC(F)=CC=C1C1=NOC2=CC(Cl)=CC=C12 CRBBEKVLXLCCMY-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- AWSHJABBFJHIDH-UHFFFAOYSA-N 2-[2-(1,2-benzoxazol-3-yl)phenyl]-2-methylpent-4-enoic acid Chemical compound C=CCC(C)(C(O)=O)C1=CC=CC=C1C1=NOC2=CC=CC=C12 AWSHJABBFJHIDH-UHFFFAOYSA-N 0.000 description 2
- KJCDMXWQQNCOPE-UHFFFAOYSA-N 2-[[2-(1,2-benzoxazol-3-yl)phenyl]methyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC1=CC=CC=C1C1=NOC2=CC=CC=C12 KJCDMXWQQNCOPE-UHFFFAOYSA-N 0.000 description 2
- YEHHOAGIGIHPBL-UHFFFAOYSA-N 2-[[2-(1,2-benzoxazol-3-yl)phenyl]methylamino]-3-phenylpropanamide Chemical compound C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1CNC(C(=O)N)CC1=CC=CC=C1 YEHHOAGIGIHPBL-UHFFFAOYSA-N 0.000 description 2
- CJUCIKJLMFVWIS-UHFFFAOYSA-N 2-bromo-5-fluorobenzaldehyde Chemical compound FC1=CC=C(Br)C(C=O)=C1 CJUCIKJLMFVWIS-UHFFFAOYSA-N 0.000 description 2
- NOUPPELZOLDUCK-UHFFFAOYSA-N 2-fluoro-n-methoxy-n-methyl-4-(trifluoromethyl)benzamide Chemical compound CON(C)C(=O)C1=CC=C(C(F)(F)F)C=C1F NOUPPELZOLDUCK-UHFFFAOYSA-N 0.000 description 2
- RHPUTIYHXQQPBX-UHFFFAOYSA-N 3-(1,2-benzoxazol-3-yl)benzaldehyde Chemical compound O=CC1=CC=CC(C=2C3=CC=CC=C3ON=2)=C1 RHPUTIYHXQQPBX-UHFFFAOYSA-N 0.000 description 2
- DSOLAYKMBAIBMT-UHFFFAOYSA-N 3-[2-(1-azidobut-3-ynyl)phenyl]-1,2-benzoxazole Chemical compound [N-]=[N+]=NC(CC#C)C1=CC=CC=C1C1=NOC2=CC=CC=C12 DSOLAYKMBAIBMT-UHFFFAOYSA-N 0.000 description 2
- XRMNXSCMCIZTDA-UHFFFAOYSA-N 3-[2-(1-azidoethyl)phenyl]-1,2-benzoxazole Chemical compound [N-]=[N+]=NC(C)C1=CC=CC=C1C1=NOC2=CC=CC=C12 XRMNXSCMCIZTDA-UHFFFAOYSA-N 0.000 description 2
- POCCWZYCZJRTQM-UHFFFAOYSA-N 3-phenyl-1,2-benzoxazole Chemical compound C1=CC=CC=C1C1=NOC2=CC=CC=C12 POCCWZYCZJRTQM-UHFFFAOYSA-N 0.000 description 2
- JPUSSXAJGZPWFC-UHFFFAOYSA-N 4-fluoro-2-(5-fluoro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound FC1=CC=C(C=O)C(C=2C3=CC(F)=CC=C3ON=2)=C1 JPUSSXAJGZPWFC-UHFFFAOYSA-N 0.000 description 2
- NXAMQNZFUKJXAE-UHFFFAOYSA-N 5-fluoro-2-(5-fluoro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound O=CC1=CC(F)=CC=C1C1=NOC2=CC=C(F)C=C12 NXAMQNZFUKJXAE-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- OAWIBELLDDTBQI-UHFFFAOYSA-N C.BrC1=C(C=CC=C1)C12OCC(CO1)(CO2)C Chemical compound C.BrC1=C(C=CC=C1)C12OCC(CO1)(CO2)C OAWIBELLDDTBQI-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 238000005642 Gabriel synthesis reaction Methods 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- JHFMTEKQJGALPU-UHFFFAOYSA-N [2-(1,2-benzoxazol-3-yl)phenyl]methanamine;hydrochloride Chemical compound Cl.NCC1=CC=CC=C1C1=NOC2=CC=CC=C12 JHFMTEKQJGALPU-UHFFFAOYSA-N 0.000 description 2
- OHYLHVJPGXOWIZ-UHFFFAOYSA-N [2-(diethoxymethyl)-4-fluorophenyl]-(2,5-difluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC(F)=CC=C1C(=O)C1=CC(F)=CC=C1F OHYLHVJPGXOWIZ-UHFFFAOYSA-N 0.000 description 2
- DEUBFGMRUMBUBG-UHFFFAOYSA-N [2-(diethoxymethyl)-4-fluorophenyl]-(2-fluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC(F)=CC=C1C(=O)C1=CC=CC=C1F DEUBFGMRUMBUBG-UHFFFAOYSA-N 0.000 description 2
- XWKCOOSOTMQMLV-UHFFFAOYSA-N [2-(diethoxymethyl)-5-fluorophenyl]-(2,5-difluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC=C(F)C=C1C(=O)C1=CC(F)=CC=C1F XWKCOOSOTMQMLV-UHFFFAOYSA-N 0.000 description 2
- LWLFHYJBPHZTBZ-UHFFFAOYSA-N [2-(diethoxymethyl)-5-fluorophenyl]-(2-fluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC=C(F)C=C1C(=O)C1=CC=CC=C1F LWLFHYJBPHZTBZ-UHFFFAOYSA-N 0.000 description 2
- OEETZXCOMYWIRN-UHFFFAOYSA-N [2-(diethoxymethyl)phenyl]-(2,4-difluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC=CC=C1C(=O)C1=CC=C(F)C=C1F OEETZXCOMYWIRN-UHFFFAOYSA-N 0.000 description 2
- PKTBXSWGSBLVDT-UHFFFAOYSA-N [2-(diethoxymethyl)phenyl]-(2,5-difluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC=CC=C1C(=O)C1=CC(F)=CC=C1F PKTBXSWGSBLVDT-UHFFFAOYSA-N 0.000 description 2
- NXLBBFWXBPNBIV-UHFFFAOYSA-N [2-(diethoxymethyl)phenyl]-[2-(propan-2-ylideneamino)oxyphenyl]methanone Chemical compound CCOC(OCC)C1=CC=CC=C1C(=O)C1=CC=CC=C1ON=C(C)C NXLBBFWXBPNBIV-UHFFFAOYSA-N 0.000 description 2
- YXBCNYAUIKVHCT-UHFFFAOYSA-N [4-chloro-2-(diethoxymethyl)phenyl]-(2-fluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC(Cl)=CC=C1C(=O)C1=CC=CC=C1F YXBCNYAUIKVHCT-UHFFFAOYSA-N 0.000 description 2
- LVLGOFCAKHPSNE-UHFFFAOYSA-N [4-chloro-2-(diethoxymethyl)phenyl]-(4-chloro-2-fluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC(Cl)=CC=C1C(=O)C1=CC=C(Cl)C=C1F LVLGOFCAKHPSNE-UHFFFAOYSA-N 0.000 description 2
- RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 2
- 239000003377 acid catalyst Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 238000010533 azeotropic distillation Methods 0.000 description 2
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 2
- 150000008366 benzophenones Chemical class 0.000 description 2
- 229960004217 benzyl alcohol Drugs 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- 229940117975 chromium trioxide Drugs 0.000 description 2
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- VGAOWLDYXGZTPH-UHFFFAOYSA-N ethyl 2-[2-(1,2-benzoxazol-3-yl)phenyl]-2-methylpent-4-enoate Chemical compound CCOC(=O)C(C)(CC=C)C1=CC=CC=C1C1=NOC2=CC=CC=C12 VGAOWLDYXGZTPH-UHFFFAOYSA-N 0.000 description 2
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- GMIQHRLTWCTQSZ-UHFFFAOYSA-N n-benzhydryl-1-[2-(1,2-benzoxazol-3-yl)phenyl]methanimine Chemical compound C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C=NC(C=1C=CC=CC=1)C1=CC=CC=C1 GMIQHRLTWCTQSZ-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 230000036385 rapid eye movement (rem) sleep Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000005932 reductive alkylation reaction Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 238000010532 solid phase synthesis reaction Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229940075966 (+)- menthol Drugs 0.000 description 1
- NOOLISFMXDJSKH-AEJSXWLSSA-N (+)-menthol Chemical compound CC(C)[C@H]1CC[C@H](C)C[C@@H]1O NOOLISFMXDJSKH-AEJSXWLSSA-N 0.000 description 1
- MFOVJVCJIWVUAE-WMQZXYHMSA-N (1R)-1-[2-(1,2-benzoxazol-3-yl)-4-fluorophenyl]but-3-en-1-amine (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C=CC[C@@H](N)C1=CC=C(F)C=C1C1=NOC2=CC=CC=C12 MFOVJVCJIWVUAE-WMQZXYHMSA-N 0.000 description 1
- JOUIIVTUJAFSNJ-WMQZXYHMSA-N (1R)-1-[2-(1,2-benzoxazol-3-yl)-5-fluorophenyl]but-3-en-1-amine (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C=CC[C@@H](N)C1=CC(F)=CC=C1C1=NOC2=CC=CC=C12 JOUIIVTUJAFSNJ-WMQZXYHMSA-N 0.000 description 1
- AYDSLXXUAYWCBG-OAHLLOKOSA-N (1r)-1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine Chemical compound C=CC[C@@H](N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 AYDSLXXUAYWCBG-OAHLLOKOSA-N 0.000 description 1
- AYDSLXXUAYWCBG-HNNXBMFYSA-N (1s)-1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine Chemical compound C=CC[C@H](N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 AYDSLXXUAYWCBG-HNNXBMFYSA-N 0.000 description 1
- HGIQFKOCBOTADE-RSAXXLAASA-N (1s)-1-[2-(6-chloro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C=CC[C@H](N)C1=CC=CC=C1C1=NOC2=CC(Cl)=CC=C12 HGIQFKOCBOTADE-RSAXXLAASA-N 0.000 description 1
- BEHBHYYPTOHUHX-UHFFFAOYSA-N (2-bromophenyl) acetate Chemical compound CC(=O)OC1=CC=CC=C1Br BEHBHYYPTOHUHX-UHFFFAOYSA-N 0.000 description 1
- NLQMSBJFLQPLIJ-UHFFFAOYSA-N (3-methyloxetan-3-yl)methanol Chemical compound OCC1(C)COC1 NLQMSBJFLQPLIJ-UHFFFAOYSA-N 0.000 description 1
- AVMHMVJVHYGDOO-NSCUHMNNSA-N (e)-1-bromobut-2-ene Chemical compound C\C=C\CBr AVMHMVJVHYGDOO-NSCUHMNNSA-N 0.000 description 1
- FQDIANVAWVHZIR-UPHRSURJSA-N (z)-1,4-dichlorobut-2-ene Chemical compound ClC\C=C/CCl FQDIANVAWVHZIR-UPHRSURJSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 1
- GYPSOQXGUMIDHK-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n-(2-phenylethyl)but-3-en-1-amine Chemical compound C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C(CC=C)NCCC1=CC=CC=C1 GYPSOQXGUMIDHK-UHFFFAOYSA-N 0.000 description 1
- CQJXOOHZZUZJLA-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n-benzylbut-3-en-1-amine Chemical compound C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C(CC=C)NCC1=CC=CC=C1 CQJXOOHZZUZJLA-UHFFFAOYSA-N 0.000 description 1
- NRTOHUDSKDODNQ-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n-methyl-2-phenylethanamine;hydrochloride Chemical compound Cl.C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C(NC)CC1=CC=CC=C1 NRTOHUDSKDODNQ-UHFFFAOYSA-N 0.000 description 1
- MFOHBIQMJQLTBF-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n-methylbut-3-en-1-amine Chemical compound C=CCC(NC)C1=CC=CC=C1C1=NOC2=CC=CC=C12 MFOHBIQMJQLTBF-UHFFFAOYSA-N 0.000 description 1
- QCVIRLPMPWMQPU-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n-methylmethanamine;hydrochloride Chemical compound Cl.CNCC1=CC=CC=C1C1=NOC2=CC=CC=C12 QCVIRLPMPWMQPU-UHFFFAOYSA-N 0.000 description 1
- AYDSLXXUAYWCBG-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine Chemical compound C=CCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 AYDSLXXUAYWCBG-UHFFFAOYSA-N 0.000 description 1
- STXXHVIERRTTMA-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-yn-1-amine Chemical compound C#CCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 STXXHVIERRTTMA-UHFFFAOYSA-N 0.000 description 1
- SFZZDZHYEXQGAM-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]pentan-1-amine Chemical compound CCCCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 SFZZDZHYEXQGAM-UHFFFAOYSA-N 0.000 description 1
- GUFCVRPABUNDAS-UHFFFAOYSA-N 1-[2-(1-methylindazol-3-yl)phenyl]but-3-en-1-amine Chemical compound C12=CC=CC=C2N(C)N=C1C1=CC=CC=C1C(N)CC=C GUFCVRPABUNDAS-UHFFFAOYSA-N 0.000 description 1
- RKQOJGJWCZENQD-UHFFFAOYSA-N 1-[2-(1-methylindazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(C)N=C1C1=CC=CC=C1C(N)CC=C RKQOJGJWCZENQD-UHFFFAOYSA-N 0.000 description 1
- HEICKJFKEBRYFH-UHFFFAOYSA-N 1-[2-(6-chloro-1,2-benzoxazol-3-yl)phenyl]but-3-yn-1-amine Chemical compound C#CCC(N)C1=CC=CC=C1C1=NOC2=CC(Cl)=CC=C12 HEICKJFKEBRYFH-UHFFFAOYSA-N 0.000 description 1
- LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 1
- SFOYQZYQTQDRIY-UHFFFAOYSA-N 1-chloro-3-iodopropane Chemical compound ClCCCI SFOYQZYQTQDRIY-UHFFFAOYSA-N 0.000 description 1
- 125000006021 1-methyl-2-propenyl group Chemical group 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- FALCMQXTWHPRIH-UHFFFAOYSA-N 2,3-dichloroprop-1-ene Chemical compound ClCC(Cl)=C FALCMQXTWHPRIH-UHFFFAOYSA-N 0.000 description 1
- DWXSYDKEWORWBT-UHFFFAOYSA-N 2-(2-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1Br DWXSYDKEWORWBT-UHFFFAOYSA-N 0.000 description 1
- RFPBUXOVSZEMSW-UHFFFAOYSA-N 2-(2-bromophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1Br RFPBUXOVSZEMSW-UHFFFAOYSA-N 0.000 description 1
- RXWOHFUULDINMC-UHFFFAOYSA-N 2-(3-nitrothiophen-2-yl)acetic acid Chemical compound OC(=O)CC=1SC=CC=1[N+]([O-])=O RXWOHFUULDINMC-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- FZKIUZJAGILULP-UHFFFAOYSA-N 2-[6-(trifluoromethyl)-1,2-benzoxazol-3-yl]benzaldehyde Chemical compound N=1OC2=CC(C(F)(F)F)=CC=C2C=1C1=CC=CC=C1C=O FZKIUZJAGILULP-UHFFFAOYSA-N 0.000 description 1
- WERJQNABGXDQLP-BTJKTKAUSA-N 2-amino-2-[2-(1,2-benzoxazol-3-yl)phenyl]acetonitrile;(z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.N#CC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 WERJQNABGXDQLP-BTJKTKAUSA-N 0.000 description 1
- QGBDJNZREUSXCZ-UHFFFAOYSA-N 2-bromo-4-chloro-1-(diethoxymethyl)benzene Chemical compound CCOC(OCC)C1=CC=C(Cl)C=C1Br QGBDJNZREUSXCZ-UHFFFAOYSA-N 0.000 description 1
- AJOAHIKYBSZIEV-UHFFFAOYSA-N 2-bromo-4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C(Br)=C1 AJOAHIKYBSZIEV-UHFFFAOYSA-N 0.000 description 1
- SFGFOJPGCOYQJK-UHFFFAOYSA-N 2-bromo-4-fluoro-1-methylbenzene Chemical compound CC1=CC=C(F)C=C1Br SFGFOJPGCOYQJK-UHFFFAOYSA-N 0.000 description 1
- OPZDXMCOWFPQPE-UHFFFAOYSA-N 2-bromo-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(Br)=C1 OPZDXMCOWFPQPE-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- VTUKKVHSZDBIPA-UHFFFAOYSA-N 3,5,8-trioxabicyclo[2.2.2]octane Chemical compound O1CC2COC1OC2 VTUKKVHSZDBIPA-UHFFFAOYSA-N 0.000 description 1
- FXIUNHPOEYCWEO-UHFFFAOYSA-N 3-(2-pyrrolidin-2-ylphenyl)-1,2-benzoxazole Chemical compound C1CCNC1C1=CC=CC=C1C1=NOC2=CC=CC=C12 FXIUNHPOEYCWEO-UHFFFAOYSA-N 0.000 description 1
- KBWHYRUAHXHHFO-UHFFFAOYSA-N 3-(bromomethyl)thiophene Chemical compound BrCC=1C=CSC=1 KBWHYRUAHXHHFO-UHFFFAOYSA-N 0.000 description 1
- DVNHHFOMVKVCJM-UHFFFAOYSA-N 3-[2-(1,2,3,6-tetrahydropyridin-2-yl)phenyl]-1,2-benzoxazole Chemical compound C1C=CCNC1C1=CC=CC=C1C1=NOC2=CC=CC=C12 DVNHHFOMVKVCJM-UHFFFAOYSA-N 0.000 description 1
- SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 description 1
- AJKDUJRRWLQXHM-UHFFFAOYSA-N 3-bromocyclohexene Chemical compound BrC1CCCC=C1 AJKDUJRRWLQXHM-UHFFFAOYSA-N 0.000 description 1
- KJPURSPTLWQLOM-UHFFFAOYSA-N 3-propyl-1,2-benzoxazole Chemical class C1=CC=C2C(CCC)=NOC2=C1 KJPURSPTLWQLOM-UHFFFAOYSA-N 0.000 description 1
- KFPDQYAPXSRACF-UHFFFAOYSA-N 4-(1,2-benzoxazol-3-yl)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=NOC2=CC=CC=C12 KFPDQYAPXSRACF-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- ZLPXBWMVZANJJQ-UHFFFAOYSA-N 4-chloro-2-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1F ZLPXBWMVZANJJQ-UHFFFAOYSA-N 0.000 description 1
- VUSYNHBKPCGGCI-UHFFFAOYSA-N 4-iodobut-1-ene Chemical compound ICCC=C VUSYNHBKPCGGCI-UHFFFAOYSA-N 0.000 description 1
- KBIWNQVZKHSHTI-UHFFFAOYSA-N 4-n,4-n-dimethylbenzene-1,4-diamine;oxalic acid Chemical compound OC(=O)C(O)=O.CN(C)C1=CC=C(N)C=C1 KBIWNQVZKHSHTI-UHFFFAOYSA-N 0.000 description 1
- QVXKELCLFMYEPC-UHFFFAOYSA-N 5-chloro-2-(6-chloro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound O=CC1=CC(Cl)=CC=C1C1=NOC2=CC(Cl)=CC=C12 QVXKELCLFMYEPC-UHFFFAOYSA-N 0.000 description 1
- AFQFIVONXIQANL-UHFFFAOYSA-N 6-(trifluoromethyl)-1,2-benzoxazole Chemical compound FC(F)(F)C1=CC=C2C=NOC2=C1 AFQFIVONXIQANL-UHFFFAOYSA-N 0.000 description 1
- WXVYFIRLSWWDBP-UHFFFAOYSA-N 6-chloro-1,2-benzoxazole Chemical compound ClC1=CC=C2C=NOC2=C1 WXVYFIRLSWWDBP-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 238000006824 Eschweiler-Clarke methylation reaction Methods 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 238000007167 Hofmann rearrangement reaction Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- YQLIMZPELWZLSY-UHFFFAOYSA-N OC(=O)C(O)=O.C(NCc1ccccc1-c1noc2ccccc12)c1ccccc1 Chemical compound OC(=O)C(O)=O.C(NCc1ccccc1-c1noc2ccccc12)c1ccccc1 YQLIMZPELWZLSY-UHFFFAOYSA-N 0.000 description 1
- SHOBNMHVIMCQFQ-UHFFFAOYSA-N OC(=O)C(O)=O.COc1ccccc1CNCc1ccccc1-c1noc2ccccc12 Chemical compound OC(=O)C(O)=O.COc1ccccc1CNCc1ccccc1-c1noc2ccccc12 SHOBNMHVIMCQFQ-UHFFFAOYSA-N 0.000 description 1
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 238000006085 Schmidt reaction Methods 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 238000003833 Wallach reaction Methods 0.000 description 1
- 239000003875 Wang resin Substances 0.000 description 1
- KYWWWBAUGDMAJT-UHFFFAOYSA-N [2-(1,2-benzoxazol-3-yl)phenyl]methanamine Chemical compound NCC1=CC=CC=C1C1=NOC2=CC=CC=C12 KYWWWBAUGDMAJT-UHFFFAOYSA-N 0.000 description 1
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
- PGVHQMHLQMUDPY-UHFFFAOYSA-M [Br-].CC(=C)C[Mg+] Chemical compound [Br-].CC(=C)C[Mg+] PGVHQMHLQMUDPY-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N alpha-methylbenzylalcohol Natural products CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical group C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- HYTACLVSJIFYBY-UHFFFAOYSA-N azane;dichloromethane;methanol Chemical compound N.OC.ClCCl HYTACLVSJIFYBY-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 229910000423 chromium oxide Inorganic materials 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000000537 electroencephalography Methods 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 1
- 229960004038 fluvoxamine Drugs 0.000 description 1
- 150000003948 formamides Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- JYGYEBCBALMPDC-UHFFFAOYSA-N heptane;propan-2-one Chemical compound CC(C)=O.CCCCCCC JYGYEBCBALMPDC-UHFFFAOYSA-N 0.000 description 1
- KWHDXJHBFYQOTK-UHFFFAOYSA-N heptane;toluene Chemical compound CCCCCCC.CC1=CC=CC=C1 KWHDXJHBFYQOTK-UHFFFAOYSA-N 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 238000009904 heterogeneous catalytic hydrogenation reaction Methods 0.000 description 1
- 238000009905 homogeneous catalytic hydrogenation reaction Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical group C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- 125000004245 indazol-3-yl group Chemical group [H]N1N=C(*)C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000002485 inorganic esters Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- JHKJQWFHNIOUKY-UHFFFAOYSA-N iodomethylcyclopropane Chemical compound ICC1CC1 JHKJQWFHNIOUKY-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960004873 levomenthol Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- QGEFGPVWRJCFQP-UHFFFAOYSA-M magnesium;methanidylbenzene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1=CC=CC=C1 QGEFGPVWRJCFQP-UHFFFAOYSA-M 0.000 description 1
- SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 1
- 239000004579 marble Substances 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 230000001193 melatoninergic effect Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- YHXISWVBGDMDLQ-UHFFFAOYSA-N moclobemide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCCN1CCOCC1 YHXISWVBGDMDLQ-UHFFFAOYSA-N 0.000 description 1
- 229960004644 moclobemide Drugs 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- SFHBPNGZDICHEI-UHFFFAOYSA-N n-[[2-(1,2-benzoxazol-3-yl)phenyl]methyl]-1-pyridin-3-ylmethanamine;dihydrochloride Chemical compound Cl.Cl.C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1CNCC1=CC=CN=C1 SFHBPNGZDICHEI-UHFFFAOYSA-N 0.000 description 1
- YTYDVSRVVWSROG-UHFFFAOYSA-N n-[[2-(1,2-benzoxazol-3-yl)phenyl]methyl]-2-phenylethanamine;hydrochloride Chemical compound Cl.C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1CNCCC1=CC=CC=C1 YTYDVSRVVWSROG-UHFFFAOYSA-N 0.000 description 1
- FWXABJFJEXZRDG-UHFFFAOYSA-N n-[[2-(1,2-benzoxazol-3-yl)phenyl]methyl]prop-2-en-1-amine;hydrochloride Chemical compound Cl.C=CCNCC1=CC=CC=C1C1=NOC2=CC=CC=C12 FWXABJFJEXZRDG-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000036403 neuro physiology Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- LURABKZOEVFURH-UHFFFAOYSA-N nitromethanesulfonic acid Chemical compound OS(=O)(=O)C[N+]([O-])=O LURABKZOEVFURH-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000007958 sleep Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000003420 transacetalization reaction Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical group C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 1
- 229960004688 venlafaxine Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- General Health & Medical Sciences (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP96201065 | 1996-04-19 | ||
| PCT/EP1997/001904 WO1997040027A1 (en) | 1996-04-19 | 1997-04-15 | Substituted benzylamines and their use for the treatment of depression |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL329348A1 PL329348A1 (en) | 1999-03-29 |
| PL192561B1 true PL192561B1 (pl) | 2006-11-30 |
Family
ID=8223896
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL329348A PL192561B1 (pl) | 1996-04-19 | 1997-04-15 | Podstawione benzyloaminy, ich zastosowanie i kompozycja farmaceutyczna |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP0898566B1 (hu) |
| JP (1) | JP4008033B2 (hu) |
| CN (1) | CN1139580C (hu) |
| AR (1) | AR006719A1 (hu) |
| AT (1) | ATE227278T1 (hu) |
| AU (1) | AU725847B2 (hu) |
| BR (1) | BR9708790A (hu) |
| CA (1) | CA2251820C (hu) |
| CZ (1) | CZ295747B6 (hu) |
| DE (1) | DE69716896T2 (hu) |
| DK (1) | DK0898566T3 (hu) |
| ES (1) | ES2186888T3 (hu) |
| HK (1) | HK1018271A1 (hu) |
| HU (1) | HU224637B1 (hu) |
| ID (1) | ID17723A (hu) |
| IL (1) | IL120669A (hu) |
| NO (1) | NO311976B1 (hu) |
| NZ (1) | NZ332334A (hu) |
| PL (1) | PL192561B1 (hu) |
| PT (1) | PT898566E (hu) |
| RU (1) | RU2179553C2 (hu) |
| TR (1) | TR199802104T2 (hu) |
| TW (1) | TW498070B (hu) |
| WO (1) | WO1997040027A1 (hu) |
| ZA (1) | ZA973209B (hu) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6080773A (en) * | 1997-10-14 | 2000-06-27 | Akzo Nobel, N.V. | Benzylamine derivatives which are useful in treating psychiatric disorders |
| US6342533B1 (en) * | 1998-12-01 | 2002-01-29 | Sepracor, Inc. | Derivatives of (−)-venlafaxine and methods of preparing and using the same |
| IL148622A0 (en) * | 1999-09-14 | 2002-09-12 | Aventis Pharm Prod Inc | Benzisoxazolyl-pyridoisoxazolyl-and benzthienyl-phenoxy derivatives useful as d4 antagonists |
| US7091199B1 (en) | 1999-09-14 | 2006-08-15 | Aventis Pharmaceuticals Inc. | Thienoisoxazole phenoxy unsubstituted ethyl and propyl derivatives useful as d4 antagonists |
| US7253165B2 (en) | 1999-09-14 | 2007-08-07 | Aventis Pharmaceuticals Inc. | Benzisoxazolyl-, pyridoisoxazolyl-and benzthienyl-phenoxy derivatives useful as D4 antagonists |
| US7125903B1 (en) | 1999-09-14 | 2006-10-24 | Aventis Pharmaceuticals Inc. | Thienoisoxazolyl-and thienylpyrrazolyl-phenoxy substituted propyl derivatives useful as D4 antagonists |
| GB0321538D0 (en) | 2003-09-13 | 2003-10-15 | Glaxo Group Ltd | Therapeutically useful compounds |
| EP1925305A1 (en) * | 2006-10-23 | 2008-05-28 | N.V. Organon | Ih channel inhibitors for the promotion of wakefulness |
| NZ593282A (en) * | 2008-12-24 | 2013-06-28 | Astrazeneca Ab | Ethanamine compounds and their use for treating depression |
| EP2473489B1 (en) | 2009-07-07 | 2013-08-21 | Merck Sharp & Dohme B.V. | 2-(1,2-benzisoxazol-3-yl)benzylamine derivatives |
| CN102942464B (zh) * | 2012-12-06 | 2015-04-08 | 西北师范大学 | 化合物1-(2-卤苯基)-3-甲基-丁酮-1的合成方法 |
| CN112300061B (zh) * | 2020-10-06 | 2022-02-18 | 大连理工大学 | 一种含氮杂环二芳酮化合物的制备方法 |
| GB202103008D0 (en) | 2021-03-03 | 2021-04-14 | King S College London | Compounds |
| GB202103012D0 (en) | 2021-03-03 | 2021-04-14 | King S College London | Compounds |
| GB202103017D0 (en) | 2021-03-03 | 2021-04-14 | King S College London | Compounds |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4980365A (en) * | 1987-07-13 | 1990-12-25 | Hoechst-Roussel Pharmaceuticals Inc. | N-substituted-5,6-dimethoxy-1,2-benzisoxazole-3-propanamine and related compounds as analgesic and hypotensive agents |
| FR2680366B1 (fr) * | 1991-08-13 | 1995-01-20 | Adir | Nouveaux derives d'arylethylamines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
-
1997
- 1997-04-15 ES ES97919371T patent/ES2186888T3/es not_active Expired - Lifetime
- 1997-04-15 DK DK97919371T patent/DK0898566T3/da active
- 1997-04-15 AU AU23870/97A patent/AU725847B2/en not_active Expired
- 1997-04-15 CA CA002251820A patent/CA2251820C/en not_active Expired - Lifetime
- 1997-04-15 PT PT97919371T patent/PT898566E/pt unknown
- 1997-04-15 TR TR1998/02104T patent/TR199802104T2/xx unknown
- 1997-04-15 BR BR9708790A patent/BR9708790A/pt not_active Application Discontinuation
- 1997-04-15 CN CNB971947376A patent/CN1139580C/zh not_active Expired - Lifetime
- 1997-04-15 CZ CZ19983349A patent/CZ295747B6/cs not_active IP Right Cessation
- 1997-04-15 NZ NZ332334A patent/NZ332334A/en not_active IP Right Cessation
- 1997-04-15 PL PL329348A patent/PL192561B1/pl not_active IP Right Cessation
- 1997-04-15 HU HU9901434A patent/HU224637B1/hu not_active IP Right Cessation
- 1997-04-15 ZA ZA9703209A patent/ZA973209B/xx unknown
- 1997-04-15 EP EP97919371A patent/EP0898566B1/en not_active Expired - Lifetime
- 1997-04-15 JP JP53769997A patent/JP4008033B2/ja not_active Expired - Lifetime
- 1997-04-15 DE DE69716896T patent/DE69716896T2/de not_active Expired - Lifetime
- 1997-04-15 RU RU98120691/04A patent/RU2179553C2/ru not_active IP Right Cessation
- 1997-04-15 IL IL12066997A patent/IL120669A/en not_active IP Right Cessation
- 1997-04-15 AT AT97919371T patent/ATE227278T1/de active
- 1997-04-15 WO PCT/EP1997/001904 patent/WO1997040027A1/en active IP Right Grant
- 1997-04-19 TW TW086105111A patent/TW498070B/zh not_active IP Right Cessation
- 1997-04-21 ID IDP971328A patent/ID17723A/id unknown
- 1997-04-21 AR ARP970101597A patent/AR006719A1/es active IP Right Grant
-
1998
- 1998-10-16 NO NO19984836A patent/NO311976B1/no not_active IP Right Cessation
-
1999
- 1999-08-02 HK HK99103314A patent/HK1018271A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU641005B2 (en) | Heterocyclic N-substituted derivatives, their preparation and thepharmaceutical compositions containing them | |
| US5352788A (en) | N-substituted heterocyclic derivatives | |
| PL192561B1 (pl) | Podstawione benzyloaminy, ich zastosowanie i kompozycja farmaceutyczna | |
| AU735705B2 (en) | Certain pyrazole derivatives as corticotropin-releasing factor receptor CRF 1 specific ligands | |
| JP3478852B2 (ja) | ジフェニルオキサゾール、チアゾールおよびイミダゾールのアデノシン再吸収阻害誘導体 | |
| JP7221861B2 (ja) | オルトミクソウイルス感染症を治療するのに有用な縮合三環式ピリダジノン化合物 | |
| EP1720613A2 (en) | Fused tricyclic compounds as inhibitors of 17beta-hydroxysteroid dehydrogernase 3 | |
| LU84070A1 (fr) | Derives phenylcyclobutyliques,leur procede de preparation et leur application therapeutique | |
| KR20040068286A (ko) | Ｃｂ１ 길항물질로서의 5,6-디아릴-피라진-2-아미드 유도체 | |
| CZ322592A3 (en) | 2-aminomethyl-chromans | |
| JP2009526037A (ja) | トリアゾロピリジン化合物 | |
| CA2591079A1 (en) | Bridged ring nk1 antagonists | |
| WO2014146246A1 (en) | Cycloalkyl nitrile pyrazolo pyridones as janus kinase inhibitors | |
| SK105294A3 (en) | Indole derivatives, method of their preparation, intermediates of this process, pharmaceutical agents containing these derivatives and use of these derivatives | |
| EP2800569B1 (en) | Allosteric modulators of cb1 cannabinoid receptors | |
| CN111801333B (zh) | 作为正粘病毒复制抑制剂用于治疗流感的化合物 | |
| KR20010015787A (ko) | 테트라히드로피리도피리미디논의 제3 위치 치환 유도체,그의 제조 방법 및 용도 | |
| JP2008503560A (ja) | ジアザビシクロ系のヒスタミン−３受容体アンタゴニスト | |
| EP0362941B1 (en) | 4-Methyl and 4-ethyl substituted pyrrolidin-2-ones | |
| JP6368043B2 (ja) | 三環式ラクタム化合物の製造法 | |
| KR100498823B1 (ko) | 치환된벤질아민및이를우울증의치료에사용한방법 | |
| JP4339939B2 (ja) | テトラヒドロイミダゾ〔２，１−ａ〕イソキノリン誘導体 | |
| Madkour | Simple one-step syntheses of heterocyclic systems from 2-phenyl-4-thienylmethylidene-5 (4H)-oxazolone | |
| MXPA00002601A (en) | 3-substituted tetrahydropyridopyrimidinone derivatives, method for producing the same, and their use | |
| MXPA06009686A (en) | Imidazole compounds for the treatment of neurodegenerative disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RECP | Rectifications of patent specification | ||
| LAPS | Decisions on the lapse of the protection rights |
Effective date: 20120415 |